Ebola Virus Infection Of Human Pbmcs Causes Massive Death...

[charlie]

Ebola virus infection of human PBMCs causes massive death of macrophages, CD4 and CD8 T cell sub-populations in vitro


Abstract

Ebola virus causes an often fatal disease characterized by poor immune response and high inflammatory reaction in the patients. One of the causes for poor immunity is virus-mediated apoptosis of lymphocytes in the host. In this study, we infected human PBMCs with Ebola Zaire virus and study apoptosis of different cell types using flow cytometry. We have shown that Ebola virus causes bystander death of CD4 and CD8 T cells. Cells infected with virus had 30–40% active caspase 3+, annexin-V+ and Bcl2low phenotype by day 8 PI as compared to inactivated virus-treated cells. 60–70% of the macrophages were also dead by day 8 PI and had similar phenotype. Our data also showed that virus may induce death signals in Fas+/FasL+ T lymphocytes and macrophages but did not upregulate Fas/FasL expression in these cells. Lastly, CD4, CD8 and CD14 cells were purified after infection and were studied for death signals by RNAse protection assay. We found an upregulation of TRAIL mRNA in CD4 and CD8 T cells on day 7 PI. A two-fold increase in CD4 T cells and three-fold increase in CD8 T cells were observed in TRAIL mRNA levels as compared to uninfected controls and inactive virus-treated cells. Surprisingly, we did not find any difference in TRAIL mRNA levels between infected macrophages and uninfected controls. These data suggest that Ebola virus evades the immune response by causing massive lymphocyte death. In addition, they may give an explanation on why the host is unable to produce a good antibody response in the absence of CD4 T cells.

http://www.sciencedirect.com/science/ar ... 2207000931

 

[Such_Saturation]

Re: Ebola virus infection of human PBMCs causes massive deat

Selenium and immune cell functions. II. Effect on lymphocyte-mediated cytotoxicity.

Protection from Ebola Virus Mediated by Cytotoxic T Lymphocytes Specific for the Viral Nucleoprotein

 

[LucyL]

Re: Ebola virus infection of human PBMCs causes massive deat

Mouse models suggest this lymphocyte apoptosis is irrelevent to EVD disease progression

Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis

Surprisingly, inhibiting lymphocyte apoptosis during EBOV infection did not result in improved animal survival. Furthermore, we show for the first time that hepatocyte apoptosis likely occurs in EBOV infection, and that mice lacking the proapoptotic genes Bim and Bid had reduced hepatocyte apoptosis and liver enzyme levels postinfection. Collectively, these data suggest that EBOV induces multiple proapoptotic stimuli and that blocking lymphocyte apoptosis is not sufficient to improve survival in EBOV infection. These data suggest that hepatocyte apoptosis may play a role in the pathogenesis of EBOV infection, whereas lymphocyte apoptosis appears to be nonessential for EBOV disease progression. The Journal of Immunology, 2010, 184: 327–335.

 

[Suikerbuik]

Re: Ebola virus infection of human PBMCs causes massive deat

I haven't read any of these studies but mouse are not humans, and I know that mouse macrophages do not express CD4. This slight difference could be a major difference as it seems that CD4 is somehow involved in ebola infection en resulting cell death.